We are presently attempting to determine the ability of mitogenic hormones to sensitize hypoxic and oxic plateau phase cultures of human and animal tumor cells to ionizing radiation. Part of the work concerns the influence of purified major component (MC) insulin on the radiation response. The mechanism of action of insulin may involve either an intracellular effect of its A or B chain or a membrane thiol exchange. Therefore, we are determining radiation responses of plateau phase cultures in the presence of these polypeptides as well as tripeptide with insulin-like activity. Additional radiation studies include the effect of cellular thiols on the mechanism of insulin action as well as the combined use of respiratory inhibitors and other mitogenic agents, such as the epidermal growth factor (EGF) and the phorbol esters. The respiratory inhibitors include the classical agents such as rotenone and antimycin A in addition to hypoxic cell radiosensitizing drugs, such as metronidazole and misonidazole. These drugs also influence the endogenous content of non-protein thiols. Human glioma, HeLa and HeP-2 tumor cells as well as V-79 lung cells will be used in our studies. If time permits, we will determine radiation responses of the EMT6 tumor grown in vivo but assayed in vitro by clonogenic survival.